Ternäre Übergangsmetallacetylide

Durch die Reaktion von CuI mit in flüssigem Ammoniak suspendierten A2C2 (A = K, Rb, Cs) und anschließendes Erhitzen des Rückstandes im Vakuum waren die ternären Alkalimetallkupferacetylide ACuC2 zugänglich. NaCuC2 konnte durch die Zersetzung von NaCu5(C2)3 erhalten werden. Die Kristallstrukturen wurden mittels Röntgen- und Neutronenpulverdiffraktometrie bestimmt. In NaCuC2 und beta-RbCuC2 sind [Cu(C2)2/2]-Ketten parallel zur c-Achse einer tetragonalen Elementarzelle orientiert (KAgC2-Typ, P4/mmm, Z = 1). In KCuC2, alpha-RbCuC2 und CsCuC2 verlaufen diese Ketten parallel zueinander in Schichten, die entlang der c-Achse einer tetragonalen Elementarzelle abwechselnd um 90° gedreht gestapelt sind (CsAgC2-Typ, P42/mmc, Z = 2). Raman- und 13C-MAS-NMR-Spektren von ACuC2 (A = K, Rb, Cs) zeigten die Existenz von C-C-Dreifachbindungen an. NaCu5(C2)3 konnte durch die Reaktion von NaC2H mit CuI in flüssigem Ammoniak und anschließendes Erhitzen des Rückstandes im Vakuum erhalten werden. Es besteht aus einem dreidimensionalen [Cu5(C2)3]-Polyanion mit kurzen Cu-Cu-Kontakten und Natriumionen in seinen Hohlräumen, wie Pulverdiffraktometeruntersuchungen mit Röntgen- und Synchrotron-strahlung ergaben (Pnma, Z = 4). Die Dreifachbindungen der beiden kristallographisch unabhängigen C2-Hanteln sind den Raman- und IR-Spektren zufolge geschwächt. Die Diammoniakate K2M(C2H)4 · 2 NH3 (M = Zn, Cd) wurden als Einkristalle aus KC2H und K2Zn(CN)4 bzw. Cd(NH2)2 in flüssigem Ammoniak dargestellt (I2/a, Z = 4). Es liegen tetraedrische [M(C2H)4]-Baugruppen und [K(C2H)6]- Oktaeder vor. Diese Oktaeder sind über gemeinsame Kanten zu Zick-Zack- Ketten verbunden. Ein zweites kristallographisch unabhängiges Kaliumion verknüpft diese Ketten untereinander und bindet die NH3-Moleküle. Die Komplexe A2M(C2H)4 (A = Na - Cs; M = Zn, Cd) waren durch das Entfernen des Ammoniaks aus den entsprechenden Ammoniakaten zugänglich. Während Na2M(C2H)4 röntgenamorph war und die Kristallstruktur von Cs2Zn(C2H)4 nicht gelöst werden konnte, sind alle anderen Ethinylo-Komplexe ihren Röntgenpulverdiffraktogrammen zufolge isotyp zueinander (K2Zn(C2H)4- Typ, I41/a, Z = 4). Wie in den Ammoniakaten existieren [M(C2H)4]-Tetraeder und Zick-Zack-Ketten aus [A(C2H)6]-Oktaedern. Die Raman-Spektren aller Verbindungen zeigten die Existenz von C-C-Dreifachbindungen an. Die Erdalkalimetall-Verbindungen EAM(C2H)4 (EA = Mg - Ba; M = Zn, Cd) waren röntgenamorph und konnten nur durch ihre Raman-Spektren identifiziert werden. Versuche, ternäre Acetylide der allgemeinen Zusammensetzung A2M(C2)2 (M = Zn, Cd, Pd) darzustellen, führten zu röntgenamorphen Pulvern ohne Banden in ihren Raman-Spektren

cis-Bis[N′-(4-bromo­benzo­yl)-N,N-dimethyl­thio­ureato-κ2 O,S]copper(II)

The asymmetric unit of the title compound, [Cu(C10H10BrN2OS)2], contains two independent complex mol­ecules with almost identical conformations. Two S and two O atoms form the coordination environment of the Cu atom, resulting in a slightly distorted square-planar coordination. The S atoms are in a cis configuration. The crystal structure is stabilized by weak inter­molecular C—H⋯Br hydrogen-bonding inter­actions

Nitration of Wheat Amylase Trypsin Inhibitors Increases Their Innate and Adaptive Immunostimulatory Potential in vitro

Amylase trypsin inhibitors (ATI) can be found in all gluten containing cereals and are, therefore, ingredient of basic foods like bread or pasta. In the gut ATI can mediate innate immunity via activation of the Toll-like receptor 4 (TLR4) on immune cells residing in the lamina propria, promoting intestinal, as well as extra-intestinal, inflammation. Inflammatory conditions can induce formation of peroxynitrite (ONOO−) and, thereby, endogenous protein nitration in the body. Moreover, air pollutants like ozone (O3) and nitrogen dioxide (NO2) can cause exogenous protein nitration in the environment. Both reaction pathways may lead to the nitration of ATI. To investigate if and how nitration modulates the immunostimulatory properties of ATI, they were chemically modified by three different methods simulating endogenous and exogenous protein nitration and tested in vitro. Here we show that ATI nitration was achieved by all three methods and lead to increased immune reactions. We found that ATI nitrated by tetranitromethane (TNM) or ONOO− lead to a significantly enhanced TLR4 activation. Furthermore, in human primary immune cells, TNM nitrated ATI induced a significantly higher T cell proliferation and release of Th1 and Th2 cytokines compared to unmodified ATI. Our findings implicate a causative chain between nitration, enhanced TLR4 stimulation, and adaptive immune responses, providing major implications for public health, as nitrated ATI may strongly promote inhalative wheat allergies (baker's asthma), non-celiac wheat sensitivity (NCWS), other allergies, and autoimmune diseases. This underlines the importance of future work analyzing the relationship between endo- and exogenous protein nitration, and the rise in incidence of ATI-related and other food hypersensitivities

Comparative chromosome painting discloses homologous Segments in distantly related mammals

Comparative chromosome painting, termed ZOO-FISH, using DNA libraries from flow sorted human chromosomes 1,16,17 and X, and mouse chromosome 11 discloses the presence of syntenic groups in distantly related mammalian Orders ranging from primates (Homo sapiens), rodents (Mus musculus), even-toed ungulates (Muntiacus muntjak vaginalis and Muntiacus reevesi) and whales (Balaenoptera physalus). These mammalian Orders have evolved separately for 55-80 million years (Myr). We conclude that ZOO-FISH can be used to generate comparative chromosome maps of a large number of mammalian species

Impact of a surgical approach for implantation of durable left ventricular assist devices in patients on extracorporeal life support

Background The aim of this study was to evaluate the impact of the surgical approach on the postoperative outcome in patients who underwent left ventricular assist device (LVAD) implantation after having received veno-arterial extracorporeal life support (va-ECLS) using data from a European registry (ECLS-VAD). Five hundred and thirty-one patients were included. Methods A propensity score-adjusted outcome analysis was performed, resulting in 324 patients in the full sternotomy (FS) group and 39 in the less invasive surgery (LIS) group. Results The surgery lasted in median 236 min in the FS group versus 263 min in the LIS group (p = 0.289). The median chest tube output during the first 24 h was similar in both groups. Patients who underwent implantation with an FS required more blood products during the first 24 postoperative hours (median 16 vs. 12, p = 0.033). The incidence of revision due to bleeding was also higher (35.5 vs. 15.4%, p = 0.016). A temporary postoperative right ventricular assist device was necessary in 45.1 (FS) versus 23.1% (LIS) of patients, respectively (p = 0.067). No stroke occurred in the LIS group during the first 30 days after surgery (7.4% in the FS group). The incidence of stroke and of renal, hepatic, and respiratory failure during the follow-up was similar in both groups. The 30-day and one-year survival were similar in both groups. Conclusion LIS for implantation of a durable LVAD in patients on va-ECLS implanted for cardiogenic shock is associated with less revision due to bleeding, less administration of blood products and absence of perioperative stroke, with no impact on survival

PEDIA: prioritization of exome data by image analysis.

PURPOSE: Phenotype information is crucial for the interpretation of genomic variants. So far it has only been accessible for bioinformatics workflows after encoding into clinical terms by expert dysmorphologists. METHODS: Here, we introduce an approach driven by artificial intelligence that uses portrait photographs for the interpretation of clinical exome data. We measured the value added by computer-assisted image analysis to the diagnostic yield on a cohort consisting of 679 individuals with 105 different monogenic disorders. For each case in the cohort we compiled frontal photos, clinical features, and the disease-causing variants, and simulated multiple exomes of different ethnic backgrounds. RESULTS: The additional use of similarity scores from computer-assisted analysis of frontal photos improved the top 1 accuracy rate by more than 20-89% and the top 10 accuracy rate by more than 5-99% for the disease-causing gene. CONCLUSION: Image analysis by deep-learning algorithms can be used to quantify the phenotypic similarity (PP4 criterion of the American College of Medical Genetics and Genomics guidelines) and to advance the performance of bioinformatics pipelines for exome analysis

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes